The focus of this program is the elucidation of the structural and functional properties of principles which mediate the inflammatory components of immediate- and subacute-type immunological reactions in human lung. The leukotactic lipoxygenase metabolites of arachidonic acid and the phospholipid platelet-activating factors produced by human alveolar macrophages and blood monocytes will be analyzed in terms of the pathways of generation and the biochemical characteristics of the mediators. The activities of the purified mediators will be defined in relation to their role in recruiting and activating PMN leukocytes and platelets in pulmonary inflammatory responses. Investigations of the IgE-dependent stimulation of isolated human lung mast cells will be directed to the release of preformed macromolecular mediators, including heparin and specific enzymes, and to the generation and release of prostaglandin D2, the predominant mast cell cyclo-oxygenease metabolite of arachidonic acid. Electron microscopy will be employed in parallel with biochemical assays of mediators in order to study the morphological concomitants of the activation of human lung mast cells by IgE-dependent stimuli. The neutral peptide contractile and vaso-active mediator, which is cleaved from a plasma glycoprotein by a distinct alpha 1-anti-trypsin-inhibitable neutrophil ectoprotease, will be prepared and purified in quantities sufficient for determination of the amino acid sequence.